1. Field of the Invention
This invention relates to a class of proteoglycans having fucosylated acidic glycan side chains bound to a protein backbone which have been found to stimulate selectively proliferation of natural killer (NK) cells and/or γδT cells. They are useful as immunostimulants, e.g., in the treatment of cancer and viral infections.
2. Description of the Related Art
The proteoglycans of the invention are produced by proliferating cells, for example by sponge cells, sea urchin cells, and, in the case of higher animals (including humans), by embryonic cells and tumor cells. In the natural proteoglycan form, the compounds are large (ca. 5000 to 30,000 kD) extracellular or membrane-bound molecules having a protein backbone which is glycosylated with acidic glycan chains having an unusual polysaccharide sequence containing internal fucose. The structure of the acidic glycan side chains of the proteoglycan isolated from the marine sponge Microciona prolifera has been partially characterized (Spillmann, et al., J. Biol. Chem. (1993) 268: 13378-13387, contents incorporated herein by reference), and we have previously shown that this proteoglycan is involved in cellular aggregation (Misevic, et al., J. Biol. Chem. (1987) 262: 5870-5877; Misevic, et al., J. Biol. Chem. (1990) 265: 20577-20584; Misevic, et al., J. Biol. Chem. (1993) 268: 4922-4929, contents of all of these articles incorporated herein by reference). The previously undescribed protein backbone of the Microciona prolifera proteoglycan has now been isolated and characterized, and novel proteoglycans derived from sponges of other genera have also been characterized, as described below.
Those concerned with these and other problems recognize the need for an improved fucose containing proteoglycan or acidic glycan and their pharmaceutical use.